Modulation of Cancer by Natural Products

Many epidemiologic studies identified associations between diet and risk of cancer. These epidemiologic findings are translated into basic research projects to determine the role of dietary components in regulating cancer cell proliferation and metastasis. One team of investigators builds on traditional strengths of the Comprehensive Cancer Center of Wake Forest University in the area of lipid signaling to determine how omega-3 polyunsaturated fatty acids (PUFAs) inhibit, whereas omega-6 PUFAs stimulate, cancer cell growth. Other investigators study vitamin D and soy isoflavones, both of which inhibit cell proliferation. Of particular interest is their activity in prostate and breast cancer. These investigators discovered a synergy between vitamin D and soy isoflavones in the inhibition of cancer cell growth. The research of this group is now focused on determining the signaling mechanisms of vitamin D and soy that inhibit cell proliferation.

The Tumor Microenvironment

Cancers seldom present a homogenous environment, consisting of a variety of different cell types and with differing degrees of vascularization. Targeting different elements of the microenvironment, e.g., by inhibiting angiogenesis, has recently been a major thrust in cancer therapy. The tumor microenvironment is a broad scientific area. The research in the Tumor Progression and Recurrence Program is focused on specific cell types associated with the tumor microenvironment. These include cell types involved in vascularization (endothelial cells and mural cells), stem cells (or more conservatively, progenitor cells with stem cell-like properties), and more recently, immune and inflammatory cells in the tumor microenvironment.

Decisions of Cell Fate in Cancer

The decisions between cell survival and cell death in response to extracellular and intracellular signals are critically important both to the development of cancer and to therapy of cancer. The Tumor Progression and Recurrence Program places a strong emphasis on signaling mechanisms that determine whether cells are able to survive and proliferate or undergo cell death. Control of cell fate decisions is regulated at the level of gene expression by proteins such as p53, which is a major tumor suppressor that is often inactivated in many cancers. Investigators in the Tumor Progression and Recurrence Program study the mechanisms that inhibit p53 in cancers without defects in p53 itself.

Cell fate decisions are often mediated by signaling pathways that act through Bcl-2 family proteins, which regulate the release of proteins from mitochondria and other organelles that induce programmed cell death (apoptosis). Investigators in the Tumor Progression and Recurrence Program study the role of Bcl-2 family proteins in regulating cell death or survival in response to stress hormones, in immune cells responsible for immune clearance of tumors, and in cancers treated with novel viruses designed to lyse cancer cells without harming normal tissues (“oncolytic viruses”).

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